The long-term goal of our research is to dissect the cellular and biochemical basis of this light control of development switch. Our previous work, together with studies from others, has defined a group of evolutionary conserved COP/DET/FUS proteins forming three major protein complexes that act as light nactivatable represser of photomorphogenesis. We have established that those three complexes act within nucleus to suppress the photomorphogenic developmental pathway in darkness and light reverses this repressive action, in part by depleting COP1 nuclear accumulation. In the nucleus, COP1 complexes act as E3 ligase, physically contact and target specific transcription factors (including HY5 and HYH) for ubiquitination and proteasome mediated degradation. The activities of those transcription factors are responsible for promoting photomorphogenic development and gene expression.While CDD complex (COP10, DET1, and DDB1) works as a component of a novel CUL4-Rbx1 based E3 ligase whose activity depends on functional COP9 signalosome and positively regulates the COP1 complexes. We further established that phosphorylation events in phytochrome A and its downstream partner FHY1 play critical roles in far red light control of development and their functional interactions with COP1 complexes. Here I propose to continue our combinatorial approaches to comprehensively analyze how this regulatory network mediates light control of genome expression and development. To achieve this goal, I proposed three major complementary aspects of further research with nine specific aims. The first aspect, including Aims 1-3, is to reveal the biochemical activities underlining the functional interaction among the E3 ligase complexes and the COP9 signalosome. The second aspect, including Aims 4-6, is to understand the biochemical and molecular events defining functional interplay between the COP1 E3 ligase complexes and phytochrome A signaling pathway. The third aspect, including Aims 7-9, is to provide a whole genome level understanding on light control of gene expression and reveal the transcriptional cascade/network and chromatin remodeling events at a genomic scale. The accomplishment of these proposed objectives shall provide a comprehensive and mechanistic view of the signaling network responsible for light control of development. This should serve as an essential guidance for investigating similar biochemical entities in mammals including human.
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